Interstitial cystitis/painful bladder syndrome (IC) or Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is characterized by chronic pelvic pain and voiding dysfunction. IC or CP/CPPS remains an enigma within urology, with no known etiology or widely effective therapies. However, some IC, CP/CPPS, and depressed patients suffer bowel co-morbidities, and it is well established that the GI tract can influence bladder function, mood and sensation via pelvic organ crosstalk. Like other body sites, the gut harbors a rich microflora. Studies characterizing microbial diversity and relative abundance at a particular body site, the "microbiome," reveal that microbiomes play critical roles in normal cellular and organ function, and thus this importance is emphasized with the Human Microbiome Project (HMP), an NIH Common Fund initiative. CPPS patients suffer chronic pelvic pain and dramatically lower quality of life, yet diagnostic markers and effective therapies remain elusive for these costly syndromes. IC is a debilitating condition of pelvic pain and voiding dysfunction afflicting up to 8 million U.S. women where depression is a common co-morbidity, distinct from over-active bladder (OAB) patients lacking pain. IC etiology remains unknown, but urothelial lesions and lamina propria mast cells are associated with patient symptoms. Similarly, CP/CPPS afflicts 1 in 22 men in the U.S. with pain and voiding and sexual symptoms, again distinct from patients having only irritative voiding from lower urinary tract symptoms (LUTS). And although leukocytes are observed in prostatic fluid of some patients, the etiology of CP/CPPS also remains unknown. Hypothalamic-pituitary-adrenal axis (HPA) dysfunction has been implicated in female and male patients and cats with feline IC, and thus may be common among CPPS, but a mechanism that integrates pelvic pain, voiding dysfunction, HPA activity, and depression is lacking.